The research proposal involves the design, synthesis, and-evaluation of two types of minor groove DNA binding ligands. The distamycin- peptide hybrid ligands will bind DNA such that the peptide portion of the ligand forms an anti parallel beta-ribbon in the minor groove through an induced fit mechanism. The ligand-DNA complexes will be studied by IR, CD, Raman, and NMR spectroscopy in addition to isothermal calorimetry titration studies. The goal of the proposal is to gain a better understanding of how the beta-ribbon motif is used by proteins to bind DNA in the minor groove.